Evolutionary paths that link orthogonal pairs of binding proteins.

ABSTRACT: Some protein binding pairs exhibit extreme specificities that functionally insulate them from homologs. Such pairs evolve mostly by accumulating single-point mutations, and mutants are selected if their affinity exceeds the threshold required for function^1-4. Thus, homologous and high-specificity binding pairs bring to light an evolutionary conundrum: how does a new specificity evolve while maintaining the required affinity in each intermediate^5,6? Until now, a fully functional single-mutation path that connects two orthogonal pairs has only been described where the pairs were mutationally close thus enabling experimental enumeration of all intermediates². We present an atomistic and graph-theoretical framework for discovering low molecular strain single-mu

SUBMITTER: Avizemer Z 

PROVIDER: S-EPMC10153392 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature